Objective To investigate the effects of Gli2 on the proliferation, growth, migration, and invasion of oral cancer cells (Tca8113) at the cellular level, and to clarify the molecular mechanism of how Gli2 regulation affects the migration and invasion of oral cancer cells. Methods Small interfering ( si)RNA was used to inhibit Gli2 expression in Tca8113 cells. The effects of Gli2 on the proliferation, growth, migration, and invasion of Tca8113 cells were examined by CCK-8, plate cloning, and transwell chamber assay. Further qRT-PCR and Western blot assays were used to explore the mechanism of how Gli2 regulation effects the malignant proliferation and metastasis of Tca8113 cells. Results The mRNA and protein expression of Gli2 in oral cancer cells ( Tca8113) increased. Interference of Gli2 expression inhibited the proliferation, growth, migration, and invasion of Tca8113 cells. Further experiments showed that interfering with Gli2 expression inhibited the mRNA and protein expression of key factors in the Hedgehog ( Hh) pathway. In addition,interference of Gli2 expression significantly affected the mRNA and protein expression of key factors in epithelial mesenchymal transformation ( EMT) pathways. Conclusions Gli2 is abnormally activated during oral cancer, and interference of Gli2 expression significantly inhibits the proliferation, growth, migration, and invasion of oral cancer cells.Gli2 influences the migration and invasion of oral cancer cells by regulating the Hh and EMT pathways. This study has provided a new way to elucidate the pathogenesis of oral cancer and new perspectives on the clinical treatment of oral cancer.